目的 采用基于UPLC-Q-Exactive Orbitrap MS的代谢组学方法探索类风湿性关节炎大鼠内源性脂质代谢物在不同病程时期的变化趋势及祖师麻片对差异性代谢物的调控作用。方法 采用胶原诱导关节炎（CIA）大鼠模型，分别收集对照组、模型组及祖师麻片[0.6 g/（kg·d）]组大鼠造模前（0 d）及造模后14、21、36 d的血清样本，提取样本中脂质成分，经生物信息学分析鉴定并寻找差异性代谢物，并探讨代谢规律。结果 与对照组比较，胶原诱导的CIA大鼠脂质代谢出现明显异常，具体表现为3个酰基肉碱含量显著上升，TG碳链中碳原子个数小于58的TG含量呈现下调趋势，碳原子个数大于58的TG类物质含量显著升高。与模型组比较，祖师麻片对1种磷脂酰丝氨酸、1种神经酰胺、2种酰基肉碱、4种磷脂酰胆碱和4种三酰甘油的代谢水平有很好的调节作用。结论 类风湿性关节炎能够引发机体血清中脂质代谢紊乱，祖师麻片对部分脂质代谢物有调控作用。

Objective To explore the changed trend of endogenous lipid metabolites in rats with rheumatoid arthritis during different disease periods and the regulation of Zushima Tablets on differential metabolites based on UPLC-Q-Exactive Orbitrap MS. Methods The collagen-induced arthritis (CIA) rats were established using bovine type Ⅱ collagen. The serum samples were collected before (0 d) and 14, 21, and 36 d after model construction from control, model, and Zushima Tablets groups[0.6 g/(kg·d)], respectively. The lipids were extracted and identified by bioinformatics analysis to find the lipid differential metabolites. Results It was obviously observed that lipid metabolism disordered in CIA rats compared with the control group. The content of three acylcarnitines was increased significantly while the level of TG showed a downward trend in the CIA model group when the TG carbon chain was shorter than 58 carbon atoms. To the opposite, the content of TG substances with atomic number greater than fifty-eight in the model group was significantly higher than that of the control group. Zushima tablet obviously regulated the metabolism levels of a phosphatidylserine, a ceramide, two acylcarnitines, four phosphatidylcholines, and four triglycerides. Conclusion This study demonstrated that rheumatoid arthritis caused the disorder of lipid metabolism while Zushima Tablets had regulatory effects on some lipid metabolites.

国家自然科学基金资助项目（81273655）；江苏省研究生科研与实践创新计划项目（KYCX17_1323）